Within this application several publications are referenced by Arabic numerals within parentheses. Full citations for these references may be found at the end of the specification immediately preceding the claims. The disclosures of these publications in their entirety are hereby incorporated by reference into this application in order to more fully describe the state of the art to which this invention pertains.
Current scientific literature reveals that inflammatory mediators initiate a biochemical chain of events that increase capillary permeability. Under such circumstances the separation of capillary endothelial junctions cannot keep infused colloids such as serum albumin, Dextran-40, and particular intracapillary fluids within the vessel.
Colloids such as serum albumin escape into the interstitium creating a nonfunctional "third space", the volume of which increases as albumin leakage increases. This leakage widens capillary-cellular distances, creating problems of poor diffusion and transport between the circulatory system and the functional cells (i.e. the cells within the organ). The wider the distances between the functional cells and the capillaries, the less oxygen and energy substrates are able to enter the cell and the less carbon dioxide and its acid by-products are able to leave. These events result in cellular anoxia, a cellular energy deficit, acidosis and possibly sequential organ failure.
In the past, others have approached the problem of albumin leakage and the concurrent creation of a third space through chemical or pharmacological means. The present invention approaches the problem as a biophysical phenomenon; the method employed to solve the problem involves using natural or synthetic macromolecules as sealants to inhibit the escape of albumin and other macromolecules. These macromolecules are effective because their configuration prohibits their escape through the enlarged capillary endothelial junctions.